3-41224553-T-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001904.4(CTNNB1):c.41T>C(p.Met14Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CTNNB1
NM_001904.4 missense
NM_001904.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the CTNNB1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 43 curated pathogenic missense variants (we use a threshold of 10). The gene has 15 curated benign missense variants. Gene score misZ: 3.846 (above the threshold of 3.09). Trascript score misZ: 5.712 (above the threshold of 3.09). GenCC associations: The gene is linked to severe intellectual disability-progressive spastic diplegia syndrome, exudative vitreoretinopathy, exudative vitreoretinopathy 7.
BP4
Computational evidence support a benign effect (MetaRNN=0.3140304).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTNNB1 | NM_001904.4 | c.41T>C | p.Met14Thr | missense_variant | Exon 3 of 15 | ENST00000349496.11 | NP_001895.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 12, 2022 | This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CTNNB1-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 14 of the CTNNB1 protein (p.Met14Thr). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;.;T;T;T;T;.;.;.;T;T;.;T;T;T;T;.;T;T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;D;.;.;.;.;T;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;L;L;L;L;L;.;L;L;.;.;L;L;L;.;.;.;.;L;L;.;.;.;L;.;.;L;L;.;L;.;L;.;L;L;L;L;L
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;.;.;N;.;.;.;N;.;N;N;.;.;N;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N
REVEL
Benign
Sift
Uncertain
.;D;.;.;T;.;.;.;T;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
Sift4G
Pathogenic
.;D;.;.;T;.;.;.;T;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;T
Polyphen
B;.;B;.;B;B;B;B;B;.;B;B;.;.;B;B;B;.;.;.;.;B;B;.;.;.;B;.;.;B;B;.;B;.;B;.;B;B;B;B;B
Vest4
0.76, 0.77, 0.76, 0.78, 0.74
MutPred
Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;.;.;.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);.;Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);Loss of catalytic residue at M14 (P = 0.001);
MVP
0.90
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.